Abstract The goal of this Phase II SBIR is to convert Profusa?s bulky, cabled, optical reader into a wearable, flexible, disposable, bandage-like format that conforms to the foot for continuous monitoring of tissue oxygen levels during revascularization and restenosis in patients with peripheral artery disease. PAD is a manifestation of systemic atherosclerosis that affects 10-12 million people in the U.S., with prevalence increasing with age. PAD ranges from mild (accompanied by intermittent claudication or pain with exercise) to severe (accompanied by CLI and gangrene), and is associated with high rates of amputation, mortality and poor quality of life. With the appropriate monitoring and treatment, disease progression can be halted and even reversed, but easy-to-use, accurate monitoring products to indicate when a change in therapy is needed do not exist. A tissue oxygen-monitoring tool that is minimally invasive, offers high sensitivity and stability, and could give rapid tissue measurements, would be ideal for point-of-care monitoring and remote continuous measurements. PROFUSA?s oxygen sensing technology can help salvage limbs from amputation by providing a way to measure real-time tissue oxygen levels in the ischemic limb before, during, and after treatment, thus enabling appropriate therapy to be administered in a timely fashion before advanced symptoms appear. The development of the flexible patch reader would allow for continuous wireless monitoring, giving critical patient data to doctors, patients, or other caregivers in real-time. Furthermore, this technology has the potential to be transformative, not just for PAD, but for the broad field of continuous in vivo diagnostics and mobile health monitoring. In this Phase II SBIR grant, we propose to first convert Profusa?s current optical reader into a flexible, wearable format (i.e. optical patch reader) through component redesign using novel flexible, thin-film, conformal electronics. We will then test the redesigned flexible patch reader in vitro. Lastly, the project will culminate in a clinical study to test safety, wearability (human factors) and in vivo functionality.